Criteria for monitoring intrathoracic impedance

ABSTRACT

An exemplary method includes providing information (e.g., a left atrial pressure, a NYHA class, echocardiographic information, etc.), based at least in part on the information, determining a weight and, based at least in part on the weight, determining a threshold for use in intrathoracic impedance monitoring. Such an exemplary method may include comparing an intrathoracic impedance to the threshold, comparing an intrathoracic impedance change to the threshold, or comparing a product of intrathoracic impedance and time to the threshold. Various exemplary methods, devices, systems, etc., are disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is related to U.S. patent applications: 1) Ser. No.11/269,390, filed Nov. 7, 2005, titled “Criteria for MonitoringIntrathoracic Impedance”; and 2) Ser. No. 11/269,234, filed Nov. 7,2005, titled “Criteria for Monitoring Intrathoracic Impedance”.

TECHNICAL FIELD

Subject matter presented herein generally relates to determining anappropriate criterion or criteria for monitoring intrathoracic impedanceusing an implantable device.

BACKGROUND

Heart failure patients are at a heightened risk of developing pulmonaryedema. For example, as left-side cardiac function deteriorates, leftatrial pressure can increase and cause lung capillary hypertension.Hypertension can cause fluid to accumulate first in interstitial lungspace and then in alveolar or lung airspace. In a worst case scenario,excessive or prolonged hypertension causes rupture of lung capillaries.Consequently, a need exists for techniques to monitor onset and degreeof pulmonary edema. Various exemplary technologies presented herein aimto address this need and other needs.

SUMMARY

An exemplary method includes providing information (e.g., a left atrialpressure, a NYHA class, echocardiographic information, etc.), based atleast in part on the information, determining a weight and, based atleast in part on the weight, determining a threshold for use inintrathoracic impedance monitoring. Such an exemplary method may includecomparing an intrathoracic impedance to the threshold, comparing anintrathoracic impedance change to the threshold, or comparing a productof intrathoracic impedance and time to the threshold. Various exemplarymethods, devices, systems, etc., are disclosed.

In general, the various methods, devices, systems, etc., describedherein, and equivalents thereof, are optionally suitable for use in avariety of pacing therapies and other cardiac related therapies.

BRIEF DESCRIPTION OF THE DRAWINGS

Features and advantages of the described implementations can be morereadily understood by reference to the following description taken inconjunction with the accompanying drawings.

FIG. 1 is a simplified diagram illustrating an exemplary implantabledevice in electrical communication with various leads. A suitableimplantable device may include fewer or more leads.

FIG. 2 is a functional block diagram of an exemplary implantable deviceillustrating basic elements that are configured to provide, for example,sensing, cardioversion, defibrillation, pacing stimulation or othertissue or nerve stimulation.

FIG. 3 is a plot of intrathoracic impedance versus time for a patientwith symptoms of congestive heart failure (CHF).

FIG. 4 is a series of plots of intrathoracic impedance information forvarious patients admitted for care due to CHF symptoms.

FIG. 5 is a series of plots that include a “fluid index” versus timebased on thoracic impedance measurements.

FIG. 6 is a series of plots that pertain to pulmonary edema.

FIG. 7 is a plot and exemplary tables of information related to leftatrial pressure where a weight may depend at least in part on leftatrial pressure or NYHA class.

FIG. 8 is a series of plots pertaining to a comet score fromechocardiograph information.

FIG. 9 is an exemplary plot of a weight as a function of comet score,various exemplary equations are also included.

FIG. 10 is an exemplary method for calculating a threshold for use inmonitoring intrathoracic impedance.

FIG. 11 is an exemplary system that includes a programmer forprogramming an implantable device for use in monitoring impedance.

DETAILED DESCRIPTION

The following description includes the best mode presently contemplatedfor practicing the described implementations. This description is not tobe taken in a limiting sense, but rather is made merely for the purposeof describing the general principles of the implementations. The scopeof the described implementations should be ascertained with reference tothe issued claims. In the description that follows, like numerals orreference designators will be used to reference like parts or elementsthroughout.

Overview

Various exemplary methods, devices, systems, etc., described hereinpertain to monitoring intrathoracic impedance using an implantabledevice. Various exemplary techniques are disclosed herein to determineone or more criteria to trigger an alarm or call for other action when achange or changes occur in intrathoracic impedance. Such techniquesoptionally account for various phases or underlying mechanismsassociated with pulmonary edema. Various exemplary techniques useechocardiograph information to determine one or more criteria. Aparticular technique analyzes echocardiograph comet-tails to provide ascore indicative of the presence of or the degree of pulmonary edemaand, in turn, a weight for use in determining a threshold for use inmonitoring intrathoracic impedance.

Exemplary Stimulation Device

The techniques described below are optionally implemented in connectionwith any stimulation device that is configured or configurable tostimulate and/or shock tissue.

FIG. 1 shows an exemplary stimulation device 100 in electricalcommunication with a patient's heart 102 by way of three leads 104, 106,108, suitable for delivering multi-chamber stimulation and shocktherapy. The leads 104, 106, 108 are optionally configurable fordelivery of stimulation pulses suitable for stimulation of autonomicnerves, non-myocardial tissue, other nerves, etc. In addition, thedevice 100 includes a fourth lead 110 having, in this implementation,three electrodes 144, 144′, 144″ suitable for stimulation of autonomicnerves, non-myocardial tissue, other nerves, etc. For example, this leadmay be positioned in and/or near a patient's heart or near an autonomicnerve within a patient's body and remote from the heart. As anotherexample, such a lead may be positioned within a patient's body forpurposes of impedance measurements. While four leads 104, 106, 108, 110are shown in FIG. 1, a device may have fewer or more leads.

The right atrial lead 104, as the name implies, is positioned in and/orpasses through a patient's right atrium. The right atrial lead 104optionally senses atrial cardiac signals and/or provide right atrialchamber stimulation therapy. As shown in FIG. 1, the stimulation device100 is coupled to an implantable right atrial lead 104 having, forexample, an atrial tip electrode 120, which typically is implanted inthe patient's right atrial appendage. The lead 104, as shown in FIG. 1,also includes an atrial ring electrode 121. Of course, the lead 104 mayhave other electrodes as well. For example, the right atrial leadoptionally includes a distal bifurcation having electrodes suitable forstimulation of autonomic nerves, non-myocardial tissue, other nerves,etc.

To sense atrial cardiac signals, ventricular cardiac signals and/or toprovide chamber pacing therapy, particularly on the left side of apatient's heart, the stimulation device 100 is coupled to a coronarysinus lead 106 designed for placement in the coronary sinus and/ortributary veins of the coronary sinus. Thus, the coronary sinus lead 106is optionally suitable for positioning at least one distal electrodeadjacent to the left ventricle and/or additional electrode(s) adjacentto the left atrium. In a normal heart, tributary veins of the coronarysinus include, but may not be limited to, the great cardiac vein, theleft marginal vein, the left posterior ventricular vein, the middlecardiac vein, and the small cardiac vein.

Accordingly, an exemplary coronary sinus lead 106 is optionally designedto receive atrial and ventricular cardiac signals and to deliver leftventricular pacing therapy using, for example, at least a leftventricular tip electrode 122, left atrial pacing therapy using at leasta left atrial ring electrode 124, and shocking therapy using at least aleft atrial coil electrode 126. For a complete description of a coronarysinus lead, the reader is directed to U.S. Pat. No. 5,466,254, “CoronarySinus Lead with Atrial Sensing Capability” (Helland), which isincorporated herein by reference. The coronary sinus lead 106 furtheroptionally includes electrodes for stimulation of autonomic nerves. Sucha lead may include pacing and autonomic nerve stimulation functionalityand may further include bifurcations or legs. For example, an exemplarycoronary sinus lead includes pacing electrodes capable of deliveringpacing pulses to a patient's left ventricle and at least one electrodecapable of stimulating an autonomic nerve. An exemplary coronary sinuslead (or left ventricular lead or left atrial lead) may also include atleast one electrode capable of stimulating an autonomic nerve,non-myocardial tissue, other nerves, etc., wherein such an electrode maybe positioned on the lead or a bifurcation or leg of the lead.

Stimulation device 100 is also shown in electrical communication withthe patient's heart 102 by way of an implantable right ventricular lead108 having, in this exemplary implementation, a right ventricular tipelectrode 128, a right ventricular ring electrode 130, a rightventricular (RV) coil electrode 132, and an SVC coil electrode 134.Typically, the right ventricular lead 108 is transvenously inserted intothe heart 102 to place the right ventricular tip electrode 128 in theright ventricular apex so that the RV coil electrode 132 will bepositioned in the right ventricle and the SVC coil electrode 134 will bepositioned in the superior vena cava. Accordingly, the right ventricularlead 108 is capable of sensing or receiving cardiac signals, anddelivering stimulation in the form of pacing and shock therapy to theright ventricle. An exemplary right ventricular lead may also include atleast one electrode capable of stimulating an autonomic nerve,non-myocardial tissue, other nerves, etc., wherein such an electrode maybe positioned on the lead or a bifurcation or leg of the lead.

FIG. 2 shows an exemplary, simplified block diagram depicting variouscomponents of stimulation device 100. The stimulation device 100 can becapable of treating both fast and slow arrhythmias with stimulationtherapy, including cardioversion, defibrillation, and pacingstimulation. The stimulation device can be solely or further capable ofdelivering stimuli to autonomic nerves, non-myocardial tissue, othernerves, etc. While a particular multi-chamber device is shown, it is tobe appreciated and understood that this is done for illustrationpurposes only. Thus, various techniques described herein can beimplemented in connection with any suitably configured or configurablestimulation device. Accordingly, one of skill in the art could readilyduplicate, eliminate, or disable the appropriate circuitry in anydesired combination to provide a device capable of treating theappropriate chamber(s) or regions of a patient's heart withcardioversion, defibrillation, pacing stimulation, autonomic nervestimulation, non-myocardial tissue stimulation, other nerve stimulation,etc. Further, various techniques described herein can be implemented inconjunction with an implantable device suited for monitoringintrathoracic impedance where such a device may or may not havestimulation capabilities.

Housing 200 for the implantable device 100 is often referred to as the“can”, “case” or “case electrode”, and may be programmably selected toact as the return electrode for all “unipolar” modes. Housing 200 mayfurther be used as a return electrode alone or in combination with oneor more of the coil electrodes 126, 132 and 134 for shocking purposes.Housing 200 further includes a connector (not shown) having a pluralityof terminals 201, 202, 204, 206, 208, 212, 214, 216, 218, 221 (shownschematically and, for convenience, the names of the electrodes to whichthey are connected are shown next to the terminals).

To achieve right atrial sensing and/or pacing, the connector includes atleast a right atrial tip terminal (A_(R) TIP) 202 adapted for connectionto the atrial tip electrode 120. A right atrial ring terminal (A_(R)RING) 201 is also shown, which is adapted for connection to the atrialring electrode 121. To achieve left chamber sensing, pacing and/orshocking, the connector includes at least a left ventricular tipterminal (V_(L) TIP) 204, a left atrial ring terminal (A_(L) RING) 206,and a left atrial shocking terminal (A_(L) COIL) 208, which are adaptedfor connection to the left ventricular tip electrode 122, the leftatrial ring electrode 124, and the left atrial coil electrode 126,respectively. Connection to suitable autonomic nerve stimulationelectrodes or other tissue stimulation or sensing electrodes is alsopossible via these and/or other terminals (e.g., via a nerve and/ortissue stimulation and/or sensing terminal S ELEC 221).

To support right chamber sensing, pacing, and/or shocking, the connectorfurther includes a right ventricular tip terminal (V_(R) TIP) 212, aright ventricular ring terminal (V_(R) RING) 214, a right ventricularshocking terminal (RV COIL) 216, and a superior vena cava shockingterminal (SVC COIL) 218, which are adapted for connection to the rightventricular tip electrode 128, right ventricular ring electrode 130, theRV coil electrode 132, and the SVC coil electrode 134, respectively.Connection to suitable autonomic nerve stimulation electrodes or othertissue stimulation or sensing electrodes is also possible via theseand/or other terminals (e.g., via a nerve and/or tissue stimulationand/or sensing terminal S ELEC 221).

At the core of the stimulation device 100 is a programmablemicrocontroller 220 that controls the various modes of stimulationtherapy and sensing. As is well known in the art, microcontroller 220typically includes a microprocessor, or equivalent control circuitry,designed specifically for controlling the delivery of stimulationtherapy, and may further include RAM or ROM memory, logic and timingcircuitry, state machine circuitry, and I/O circuitry. Typically,microcontroller 220 includes the ability to process or monitor inputsignals (data or information) as controlled by a program code stored ina designated block of memory. The type of microcontroller is notcritical to the described implementations. Rather, any suitablemicrocontroller 220 may be used that carries out the functions describedherein. The use of microprocessor-based control circuits for performingtiming and data analysis functions are well known in the art.

Representative types of control circuitry that may be used in connectionwith the described embodiments can include the microprocessor-basedcontrol system of U.S. Pat. No. 4,940,052 (Mann et al.), thestate-machine of U.S. Pat. Nos. 4,712,555 (Thornander et al.) and4,944,298 (Sholder), all of which are incorporated by reference herein.For a more detailed description of the various timing intervals usedwithin the stimulation device and their inter-relationship, see U.S.Pat. No. 4,788,980 (Mann et al.), also incorporated herein by reference.

FIG. 2 also shows an atrial pulse generator 222 and a ventricular pulsegenerator 224 that generate pacing stimulation pulses for delivery bythe right atrial lead 104, the coronary sinus lead 106, and/or the rightventricular lead 108 via an electrode configuration switch 226. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart the atrial and ventricular pulse generators,222 and 224, may include dedicated, independent pulse generators,multiplexed pulse generators, or shared pulse generators. The pulsegenerators 222 and 224 are controlled by the microcontroller 220 viaappropriate control signals 228 and 230, respectively, to trigger orinhibit the stimulation pulses.

Microcontroller 220 further includes timing control circuitry 232 tocontrol the timing of the stimulation pulses (e.g., pacing rate,atrioventricular (AV) delay, atrial interconduction (A-A) delay, orventricular interconduction (V-V) delay, etc.) as well as to keep trackof the timing of refractory periods, blanking intervals, noise detectionwindows, evoked response windows, alert intervals, marker channeltiming, etc., which is well known in the art.

Microcontroller 220 further includes an arrhythmia detector 234, amorphology discrimination module 236, a capture detection/sensitivitymodule 237, a pressure analysis module 238, an impedance monitoringmodule 239 and optionally an orthostatic compensator and a minuteventilation (MV) response module, the latter two are not shown in FIG.2. These components can be utilized by the stimulation device 100 fordetermining desirable times to administer various therapies, includingthose to reduce the effects of orthostatic hypotension. Theaforementioned components may be implemented in hardware as part of themicrocontroller 220, or as software/firmware instructions programmedinto the device and executed on the microcontroller 220 during certainmodes of operation.

The pressure analysis module 238 may perform a variety of tasks relatedto one or more measures of pressure and is optionally utilized by thestimulation device 100 in determining a patient's hemodynamic profile.The impedance monitoring module 239 may perform a variety of tasksrelated to impedance monitoring, as discussed in more detail below.

The pressure analysis module 238 and the impedance monitoring module 239may be implemented in hardware as part of the microcontroller 220, or assoftware/firmware instructions programmed into the device and executedon the microcontroller 220 during certain modes of operation. Theimpedance monitoring module 239 may optionally implement variousexemplary methods described herein. The impedance monitoring module 239may be responsible for implementing intrathoracic impedance monitoringand determining, selecting or adjusting settings related thereto.

The electronic configuration switch 226 includes a plurality of switchesfor connecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly,switch 226, in response to a control signal 242 from the microcontroller220, determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, combipolar, etc.) by selectively closing the appropriatecombination of switches (not shown) as is known in the art.

Atrial sensing circuits 244 and ventricular sensing circuits 246 mayalso be selectively coupled to the right atrial lead 104, coronary sinuslead 106, and the right ventricular lead 108, through the switch 226 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits, 244 and 246, may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. Switch 226determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity. The sensing circuits (e.g., 244 and 246) areoptionally capable of obtaining information indicative of tissuecapture.

Each sensing circuit 244 and 246 preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the device 100 to deal effectively withthe difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 244 and 246are connected to the microcontroller 220, which, in turn, is able totrigger or inhibit the atrial and ventricular pulse generators 222 and224, respectively, in a demand fashion in response to the absence orpresence of cardiac activity in the appropriate chambers of the heart.Furthermore, as described herein, the microcontroller 220 is alsocapable of analyzing information output from the sensing circuits 244and 246 and/or the data acquisition system 252 to determine or detectwhether capture has occurred and to program a pulse, or pulses, inresponse to such determinations. The sensing circuits 244 and 246, inturn, receive control signals over signal lines 248 and 250 from themicrocontroller 220 for purposes of controlling the gain, threshold,polarization charge removal circuitry (not shown), and the timing of anyblocking circuitry (not shown) coupled to the inputs of the sensingcircuits, 244 and 246, as is known in the art.

For arrhythmia detection, the device 100 utilizes the atrial andventricular sensing circuits, 244 and 246, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. In reference toarrhythmias, as used herein, “sensing” is reserved for the noting of anelectrical signal or obtaining data (information), and “detection” isthe processing (analysis) of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., P-waves, R-waves, and depolarization signals associated withfibrillation which are sometimes referred to as “F-waves” or“Fib-waves”) are then classified by the arrhythmia detector 234 of themicrocontroller 220 by comparing them to a predefined rate zone limit(i.e., bradycardia, normal, low rate VT, high rate VT, and fibrillationrate zones) and various other characteristics (e.g., sudden onset,stability, physiologic sensors, and morphology, etc.) in order todetermine the type of remedial therapy that is needed (e.g., bradycardiapacing, anti-tachycardia pacing, cardioversion shocks or defibrillationshocks, collectively referred to as “tiered therapy”).

Cardiac signals are also applied to inputs of an analog-to-digital (A/D)data acquisition system 252. The data acquisition system 252 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device254. The data acquisition system 252 is coupled to the right atrial lead104, the coronary sinus lead 106, the right ventricular lead 108 and/orthe nerve or other tissue stimulation lead 110 through the switch 226 tosample cardiac signals across any pair of desired electrodes.

The microcontroller 220 is further coupled to a memory 260 by a suitabledata/address bus 262, wherein the programmable operating parameters usedby the microcontroller 220 are stored and modified, as required, inorder to customize the operation of the stimulation device 100 to suitthe needs of a particular patient. Such operating parameters define, forexample, pacing pulse amplitude, pulse duration, electrode polarity,rate, sensitivity, automatic features, arrhythmia detection criteria,and the amplitude, waveshape, number of pulses, and vector of eachshocking pulse to be delivered to the patient's heart 102 within eachrespective tier of therapy. One feature of the described embodiments isthe ability to sense and store a relatively large amount of data (e.g.,from the data acquisition system 252), which data may then be used forsubsequent analysis to guide the programming of the device.

Advantageously, the operating parameters of the implantable device 100may be non-invasively programmed into the memory 260 through a telemetrycircuit 264 in telemetric communication via communication link 266 withthe external device 254, such as a programmer, transtelephonictransceiver, or a diagnostic system analyzer. The microcontroller 220activates the telemetry circuit 264 with a control signal 268. Thetelemetry circuit 264 advantageously allows intracardiac electrogramsand status information relating to the operation of the device 100 (ascontained in the microcontroller 220 or memory 260) to be sent to theexternal device 254 through an established communication link 266.

The stimulation device 100 can further include a physiologic sensor 270,commonly referred to as a “rate-responsive” sensor because it istypically used to adjust pacing stimulation rate according to theexercise state of the patient. However, the physiological sensor 270 mayfurther be used to detect changes in cardiac output (see, e.g., U.S.Pat. No. 6,314,323, entitled “Heart stimulator determining cardiacoutput, by measuring the systolic pressure, for controlling thestimulation”, to Ekwall, issued Nov. 6, 2001, which discusses a pressuresensor adapted to sense pressure in a right ventricle and to generate anelectrical pressure signal corresponding to the sensed pressure, anintegrator supplied with the pressure signal which integrates thepressure signal between a start time and a stop time to produce anintegration result that corresponds to cardiac output), changes in thephysiological condition of the heart, or diurnal changes in activity(e.g., detecting sleep and wake states). Accordingly, themicrocontroller 220 responds by adjusting the various pacing parameters(such as rate, AV Delay, V-V Delay, etc.) at which the atrial andventricular pulse generators, 222 and 224, generate stimulation pulses.

Pressure sensors for sensing left atrial pressure are discussed in U.S.Patent Application US2003/0055345 A1, to Eigler et al., which isincorporated by reference herein. The discussion pertains to a pressuretransducer permanently implantable within the left atrium of thepatient's heart and operable to generate electrical signals indicativeof fluid pressures within the patient's left atrium. According to Eigleret al., the pressure transducer is connected to a flexible electricallead, which is connected in turn to electrical circuitry, which includesdigital circuitry for processing electrical signals. Noted positions ofthe transducer include within the left atrium, within a pulmonary vein,within the left atrial appendage and in the septal wall. Control of oracquisition of information from a pressure sensor is optionally by thepressure module 238. Such information is optionally used by theimpedance monitoring module 239, for example, to determine one or morecriteria related to monitoring intrathoracic impedance.

The exemplary device 100 optionally includes a connector capable ofconnecting a lead that includes a pressure sensor. For example, theconnector 221 optionally connects to a pressure sensor capable ofreceiving information pertaining to chamber pressures or otherpressures. Pressure information is optionally processed or analyzed bythe pressure analysis module 238 and optionally used by the impedancemonitoring module 239.

A study by Hofmann et al., “Simultaneous measurement of pulmonary venousflow by intravascular catheter Doppler velocimetry and transesophagealDoppler echocardiography: relation to left atrial pressure and leftatrial and left ventricular function”, J Am Coll Cardiol. 1995 July;26(1):239-49, used a “microtip” pressure transducer and noted that meanleft atrial pressure was strongly correlated with the ratio of systolicto diastolic peak velocity, systolic velocity-time integral, time tomaximal flow velocity and the ratio of systolic to diastolic flowduration.

Commercially available pressure transducers include those marketed byMillar Instruments (Houston, Tex.) under the mark MIKROTIP®. A study byShioi et al., “Rapamycin Attenuates Load-Induced Cardiac Hypertrophy inMice”, Circulation 2003; 107:1664, measured left ventricular pressuresin mice using a Millar pressure transducer inserted through the LV apexand secured in the LV apex with a purse-string suture using 5-0 silk.Various exemplary methods, devices, systems, etc., described hereinoptionally use such a pressure transducer to measure pressures in thebody (e.g., chamber of heart, vessel, etc.).

In various exemplary methods, while direct measurement of pulmonaryartery diastolic pressure would be helpful, one or more surrogate oralternative measurements (e.g., LA pressure, right ventricular outflowtract pressure, etc.) may be used and, where appropriate or desirable,such measures may be used to estimate pulmonary artery diastolicpressure.

While shown as being included within the stimulation device 100, it isto be understood that the physiologic sensor 270 may also be external tothe stimulation device 100, yet still be implanted within or carried bythe patient. Examples of physiologic sensors that may be implemented indevice 100 include known sensors that, for example, sense pressure,respiration rate, pH of blood, ventricular gradient, cardiac output,preload, afterload, contractility, and so forth. Another sensor that maybe used is one that detects activity variance, wherein an activitysensor is monitored diurnally to detect the low variance in themeasurement corresponding to the sleep state. For a complete descriptionof the activity variance sensor, the reader is directed to U.S. Pat. No.5,476,483 (Bornzin et al.), issued Dec. 19, 1995, which patent is herebyincorporated by reference.

Other sensors may be used, including, but not limited to, oxygensensors. Technology exists for lead-based oximeters. For example, astudy by Tsukada et al., “Development of catheter-type optical oxygensensor and applications to bioinstrumentation,” Biosens Bioelectron,2003 Oct. 15; 18(12):1439-45, reported use of a catheter-type opticaloxygen sensor based on phosphorescence lifetime.

The exemplary device 100 optionally includes a connector capable ofconnecting a lead that includes a sensor for sensing pressure, oxygeninformation, etc. For example, the connector 221 optionally connects toa sensor for sensing information related to pressure or blood oxygenconcentration. Such information is optionally processed or analyzed bythe pressure analysis module 238, the impedance monitoring module 239,or other module.

The physiological sensors 270 optionally include sensors for detectingmovement and minute ventilation in the patient. The physiologicalsensors 270 may include a position sensor and/or a minute ventilation(MV) sensor to sense minute ventilation, which is defined as the totalvolume of air that moves in and out of a patient's lungs in a minute.Signals generated by the position sensor and MV sensor are passed to themicrocontroller 220 for analysis in determining whether to adjust thepacing rate, etc. The microcontroller 220 monitors the signals forindications of the patient's position and activity status, such aswhether the patient is climbing upstairs or descending downstairs orwhether the patient is sitting up after lying down.

The stimulation device 100 optionally includes circuitry capable ofsensing heart sounds and/or vibration associated with events thatproduce heart sounds. Such circuitry may include an accelerometer asconventionally used for patient position and/or activity determinations.Accelerometers typically include two or three sensors aligned alongorthogonal axes. For example, a commercially availablemicro-electromechanical system (MEMS) marketed as the ADXL202 by AnalogDevices, Inc. (Norwood, Mass.) has a mass of about 5 grams and a 14 leadCERPAK (approx. 10 mm by 10 mm by 5 mm or a volume of approx. 500 mm³).The ADXL202 MEMS is a dual-axis accelerometer on a single monolithicintegrated circuit and includes polysilicon springs that provide aresistance against acceleration forces. The term MEMS has been definedgenerally as a system or device having micro-circuitry on a tiny siliconchip into which some mechanical device such as a mirror or a sensor hasbeen manufactured. The aforementioned ADXL202 MEMS includesmicro-circuitry and a mechanical oscillator.

While an accelerometer may be included in the case of an implantablepulse generator device, alternatively, an accelerometer communicateswith such a device via a lead or through electrical signals conducted bybody tissue and/or fluid. In the latter instance, the accelerometer maybe positioned to advantageously sense vibrations associated with cardiacevents. For example, an epicardial accelerometer may have improvedsignal to noise for cardiac events compared to an accelerometer housedin a case of an implanted pulse generator device.

The stimulation device 100 additionally includes a battery 276 thatprovides operating power to all of the circuits shown in FIG. 2. For thestimulation device 100, which employs shocking therapy, the battery 276is capable of operating at low current drains for long periods of time(e.g., preferably less than 10 μA), and is capable of providinghigh-current pulses (for capacitor charging) when the patient requires ashock pulse (e.g., preferably, in excess of 2 A, at voltages above 200V, for periods of 10 seconds or more). The battery 276 also desirablyhas a predictable discharge characteristic so that elective replacementtime can be detected.

The stimulation device 100 can further include magnet detectioncircuitry (not shown), coupled to the microcontroller 220, to detectwhen a magnet is placed over the stimulation device 100. A magnet may beused by a clinician to perform various test functions of the stimulationdevice 100 and/or to signal the microcontroller 220 that the externalprogrammer 254 is in place to receive or transmit data to themicrocontroller 220 through the telemetry circuits 264. Trigger IEGMstorage also can be achieved by magnet.

The stimulation device 100 further includes an impedance measuringcircuit 278 that is enabled by the microcontroller 220 via a controlsignal 280. The known uses for an impedance measuring circuit 278include, but are not limited to, lead impedance surveillance during theacute and chronic phases for proper lead positioning or dislodgement;detecting operable electrodes and automatically switching to an operablepair if dislodgement occurs; measuring respiration or minuteventilation; measuring thoracic impedance for determining shockthresholds (HF indications—pulmonary edema and other factors); detectingwhen the device has been implanted; measuring stroke volume; anddetecting the opening of heart valves, etc. The impedance measuringcircuit 278 is advantageously coupled to the switch 226 so that anydesired electrode may be used.

The impedance measuring circuit 278 may provide for acquisition ofintrathoracic impedance measurements. For example, an impedancemeasurement between a cardiac electrode (e.g., of one of the leads 104,106, 108) and a case electrode of the device 100 may be acquired andused by the impedance monitoring module 239. Of course, other electrodeconfigurations are possible. Impedance measurements may rely on bipolaror other multi-polar configurations. As described herein, intrathoracicimpedance includes intracardiac impedance. Intracardiac impedancepertains to impedance primarily in or across the heart, for example,measured using two or more electrodes positioned in the heart or avessel of the heart (e.g., epicardial vein, etc.).

In the case where the stimulation device 100 is intended to operate asan implantable cardioverter/defibrillator (ICD) device, it detects theoccurrence of an arrhythmia, and automatically applies an appropriatetherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the microcontroller 220 further controls a shocking circuit282 by way of a control signal 284. The shocking circuit 282 generatesshocking pulses in a range of joules, for example, conventionally up toabout 40 J, as controlled by the microcontroller 220. Such shockingpulses are applied to the patient's heart 102 through at least twoshocking electrodes, and as shown in this embodiment, selected from theleft atrial coil electrode 126, the RV coil electrode 132, and/or theSVC coil electrode 134. As noted above, the housing 200 may act as anactive electrode in combination with the RV electrode 132, or as part ofa split electrical vector using the SVC coil electrode 134 or the leftatrial coil electrode 126 (i.e., using the RV electrode as a commonelectrode).

Cardioversion level shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range ofapproximately 5 J to approximately 40 J), delivered asynchronously(since R-waves may be too disorganized), and pertaining exclusively tothe treatment of fibrillation. Accordingly, the microcontroller 220 iscapable of controlling the synchronous or asynchronous delivery of theshocking pulses.

In low-energy cardioversion, an ICD device typically delivers acardioversion stimulus (e.g., 0.1 J, etc.) synchronously with a QRScomplex; thus, avoiding the vulnerable period of the T wave and avoidingan increased risk of initiation of VF. In general, if antitachycardiapacing or cardioversion fails to terminate a tachycardia, then, forexample, after a programmed time interval or if the tachycardiaaccelerates, the ICD device initiates defibrillation therapy.

While an ICD device may reserve defibrillation as a latter tier therapy,it may use defibrillation as a first-tier therapy for VF. In general, anICD device does not synchronize defibrillation therapy with any givenportion of a ECG. Again, defibrillation therapy typically involveshigh-energy shocks (e.g., 5 J to 40 J), which can include monophasic orunidirectional and/or biphasic or bidirectional shock waveforms.Defibrillation may also include delivery of pulses over two currentpathways.

FIG. 3 shows a plot 300 of impedance versus time, specifically daysbefore hospitalization of a patient. At 14 days prior tohospitalization, a relative impedance baseline is determined to be about78 ohms; whereas, at time of hospitalization, impedance is about 60ohms. As discussed further below, the impedance does not necessarilydecrease in a linear manner from the baseline value to the CHF admissionvalue. The data of the plot 300 suggest that a significant decrease inimpedance occurred around −12 days followed by a substantially lineardecrease from about −12 days to about −7 days. Thus, a decrease inimpedance may result from varying mechanisms or phases (e.g., an onsetphase followed by one or more subsequent phases).

FIG. 4 shows a series of impedance-related plots 400, more specifically,two plots 410, 430 of impedance changes over time. The plot 410 includesimpedance information from a series of patients. According to the plot410, impedance reduction commenced an average of 10.4+/−7.8 days aheadof various symptoms (i.e., 13.4 days−3.0 days). The standard deviationyields a range for the series of patients from 18.2 days prior tosymptoms to 2.6 days prior to symptoms. Thus, a patient dependence issuggested.

The plot 420 includes impedance information from a series of patients.According to the plot 420, the average impedance decreased from arelative baseline value to a lesser value on the day before admissionrelated to various symptoms. The average relative baseline impedance ofabout 74 ohms decreased to about 66 ohms. In terms of percentagereduction, the impedance decreased by 11.4+/−5.9% for an average periodof 13.5+/−8.1 days. The standard deviation yields a percentage reductionrange for the series of patients from 17.3% to 5.5% for a range of daysof 21.6 days to 5.4 days. Thus, as already mentioned with respect to theplot 410, a patient dependence is suggested.

FIG. 5 shows a scheme 500 that uses a “fluid index” that is based onthoracic impedance measured between a can or case electrode and a rightventricular defibrillation coil electrode. The scheme 500 is describedin a report by Cowie, “Monitoring Heart Failure using an ImplantableDevice Measuring Intrathoracic Impedance—Technical and ClinicalOverview”, Business Briefing: European Cardiology 2005, pp. 62-65. Thescheme 500 is illustrated using a plot 510 of thoracic impedance versustime and a plot 530 of fluid index versus time. According to the scheme500, the plot 510 includes a daily impedance that is the average of eachday's multiple impedance measurements and a reference impedance thatadapts slowly to daily impedance changes. The plot 530 includes thefluid index, which is the accumulation of consecutive day-to-daydifferences between the daily and the reference impedance. In the scheme500, a physician can activate the patient alert in the device and when athreshold is crossed the device will audibly alarm. Also, the fluidindex is reset if the daily impedance readings become higher than theimpedance trend to reduce the risk of an alarm when the lungs are dryingout.

As described herein, various exemplary techniques account for patientdependence to allow for more accurate patient monitoring, for example,using impedance measurements. Also described herein, various exemplarytechniques optionally rely on a multi-mechanism pulmonary edema modelwhereby impedance information may be analyzed for presence of, forexample, an initial short-term phase (hours), a subsequent longer-termphase (days) or both short-term and long-term phases.

With respect to a multi-mechanism model for pulmonary edema, FIG. 6shows a plot 610 of dry lung tissue weight and extravascular fluidweight at four hours and at 14 days after elevation of left atrialpressure in sheep, as reported by Drake and Doursout, “Pulmonary edemaand elevated left atrial pressure: four hours and beyond”, News PhysiolSci. 2002 December; 17:223-6. FIG. 6 also shows plots 620, 630 whichrepresent possible exemplary scenarios for edema.

Drake and Doursout prepared the plot 610 from data taken from a study byErdmann et al., “Effect of increased vascular pressure on lung fluidbalance in unanesthetized sheep”, Circ Res. 1975 September;37(3):271-84. Erdmann et al. observed that lymph flow reached a plateauwithin the first 4 hours of elevated left atrial pressure and, to testif lung fluid was steady after 4 hours, they maintained left atrialpressure at an elevated level for 14 days.

The report of Drake and Doursout pertains primarily to cardiogenicpulmonary edema, for example, caused by an increase in left atrialpressure when the left heart fails. An increase in left atrial pressurecan cause rapid fluid accumulation within the lung interstitial spaces;however, the report suggests that, over the following days to weeks,additional fluid may accumulate due to the deposition of excess lungconnective tissue. Thus, two phases exist wherein the latter phase isassociated with more than one mechanism, for example, as hypothesized byDrake and Doursout, left atrial hypertension-related edema andfibrosis-related edema.

Referring again to the plot 610, the data indicate that significantfluid accumulation can occur over a course of days in response toelevated left atrial pressure. Further, the data of the plot 610indicate that an increase in lung dry weight may accompany an increasein extravascular fluid. In general, if the left atrial pressure exceedsa critical level of about 25 mmHg, the volume of edema fluid willoverwhelm the capacity of the interstitial spaces and fluid will floodthe airways and alveoli. While such airway edema interferes with gasexchange and can result in death, many people live for months or yearswith modestly elevated left atrial pressure (e.g., left atrial pressureless than about 25 mmHg).

Thus, the report of Drake and Doursout suggests that sustained,subcritical left atrial pressure elevations lead to two phases of changein the lungs whereby the second phase may be associated, in part, with amechanism that acts to increase lung dry weight. In particular, thefirst phase involves acute edema that develops in the first few hours ofelevated left atrial pressure and the second phase involves a“persistent” edema associated with long-term (e.g., days or more)elevation of left atrial pressure that does generally not exceed acritical level.

As to underlying mechanisms, any heart disease that leads to increasedleft atrial pressure will cause typically some degree of pulmonaryedema; however, an increase in lung connective tissue (pulmonaryfibrosis) is common in patients with chronic heart disease. Suchfibrosis may be a typical response to the persistence of edema fluid inalmost any organ. Thus, Drake and Doursout suggest a persistent edemahypothesis whereby dry lung tissue weight should be increased due to theincrease in connective tissue within the lung after a prolonged periodof elevated left atrial pressure. According to this hypothesis, theextravascular fluid-to-dry tissue weight ratio might remain almostunchanged during a prolonged period of elevated left atrial pressure. Inthe plot 610, the data indicate that lung dry weight and extravascularfluid were each about 75% higher after 14 days versus 4 hours ofelevated left atrial pressure and thus suggest that a large amount ofedema fluid accumulated in the Erdmann et al. sheep long after the first4 hours of elevated left atrial pressure. This evidence supports thepersistent edema hypothesis.

Referring again to the plot 300 of FIG. 3, a substantial decrease inintrathoracic impedance occurs over a period of 14 days prior toadmission. However, as already mentioned, a fairly large drop inimpedance occurs around day −12. Thus, the intrathoracic impedance dataof the plot 300 may also support the persistent edema hypothesis ofDrake and Doursout or other hypothesis that accounts for fluidaccumulation over a period of days.

The plots 620, 630 of FIG. 6 show possible scenarios whereby more thanone mechanism is involved in edema. The plot 620 indicates that fluidvolume increases in part due to elevated left atrial pressure and inpart due to an increase in lung dry weight, which acts to increase fluidvolume. The plot 630 indicates that a rather abrupt increase occurs inleft atrial pressure such that lung fluid volume increases in a shortperiod of time whereas a subsequent increase occurs due to an increasein lung dry weight, which acts to increase fluid volume. Of course, anelevated left atrial pressure may exist throughout the increase in lungfluid volume.

FIG. 7 shows an approximate plot 710 of edema formation (ml/time) versusleft atrial pressure (mmHg). Lung capillary pressure in healthy humansat rest ranges between about 6 mmHg and about 10 mmHg and an increase inleft atrial pressure causes a rise in lung capillary pressure, whichdirectly affects transendothelial fluid dynamics. A sufficient rise inlung capillary pressure results in the formation of hydrostatic lungedema. Further, as left atrial pressure increases, a critical value isreached whereby edema formation reaches dangerous rates that can lead todeath in a short period of time. Such critical values may be associatedwith capillary stress failure, which may also occur in response to longperiods of “sub-critical” yet elevated left atrial pressure.

Various phases and associated mechanisms for edema have already beenmentioned. With respect to fluid location within the lungs, an elevatedleft atrial pressure generally causes excess fluid to accumulate in theinterstitial spaces of the lungs. Such interstitial fluid accumulationmay occur with few or no associated clinical symptoms. In humans, theinterstitium can only accommodate a few hundred milliliters of excessfluid so the fluid soon floods the airspaces, which in a 70 kg adultapproximates 5,000 ml. Airspace flooding is associated with profoundrespiratory distress because the acini can no longer effectivelyexchange gases. Thus, a situation may become critical (i.e., lifethreatening) even where the elevated left atrial pressure does not reachcritical values.

As indicated by the plot 710, the rate of fluid transfer to the lungsdepends on left atrial pressure. Of course, the rate of fluidaccumulation and amount of fluid accumulated depends on the rate offluid removal as well. Further, external pressure can play a role, forexample, consider high-altitude edema and positive airway pressure as aform of treatment. However, in all of these instances, left atrialpressure is a factor. In general, cardiogenic edema is associated withelevated left atrial pressure. Non-cardiogenic forms of edema may or maynot be associated with left atrial pressure. Non-cardiogenic causes ofedema may be related to a pharmaceutical, narcotic overdose,chemotherapy, salicylate intoxication, calcium antagonist overdose,hydrochlorothiazide, contrast fluids, high-altitude, neurogenic,pulmonary embolism, eclampsia, post cardioversion, post anaesthesia,post cardiopulmonary bypass, etc.

FIG. 7 also shows an exemplary table 720 and an exemplary table 730 thatinclude exemplary weights that depend on left atrial pressure. Theexemplary table 720 includes a percentage threshold (Y) column where theweight (W_(Y)) is used to adjust a threshold for use in impedancemonitoring. The threshold (Y) may be determined on the basis of manypatients. For example, data of the plots of FIG. 4 may be used todetermine an average threshold. In general, the threshold (Y) representsa particular percentage decrease in intrathoracic impedance from a basevalue that warrants triggering an alarm or other action. The threshold(Y) may be for any suitable time period and may optionally be directedto a short-term phase or a long-term phase. For example, a short-termphase may pertain to lung filling without any significant increase inlung dry weight (e.g., due to fibrosis, etc.); whereas a long-term phasemay pertain to lung filling associated with an increase in lung dryweight (e.g., due to fibrosis, etc.). Further, the threshold (Y) may bedirected to an interstitial filling phase or a subsequent airspacefilling phase. For example, the threshold (Y) may represent a percentagevalue that indicates a change from interstitial filling to airspacefilling.

The exemplary table 730 includes an ohms-days threshold (I_(OD)) columnwhere the weight (W_(I)) is used to adjust a threshold for use inimpedance monitoring. The threshold (I_(OD)) may be determined on thebasis of many patients. For example, data of the plots of FIG. 4 may beused to determine an average threshold. In general, the threshold(I_(OD)) represents a particular number of ohms-days or ohms-daysdifferential based on intrathoracic impedance measurements that warrantstriggering an alarm or other action. The threshold (I_(OD)) may be forany suitable time period and may optionally be directed to a short-termphase or a long-term phase. For example, a short-term phase may pertainto lung filling without any significant increase in lung dry weight(e.g., due to fibrosis, etc.); whereas a long-term phase may pertain tolung filling associated with an increase in lung dry weight (e.g., dueto fibrosis, etc.). Further, the threshold (I_(OD)) may be directed toan interstitial filling phase or a subsequent airspace filling phase.For example, the threshold (I_(OD)) may represent a percentage valuethat indicates a change from interstitial filling to airspace filling.

-   -   CHF has been classified by the New York Heart Association (NYHA)        into four classes of progressively worsening symptoms and        exercise capacity. Class I corresponds to no limitation wherein        ordinary physical activity does not cause undue fatigue,        shortness of breath, or palpitation. Class II corresponds to        slight limitation of physical activity wherein such patients are        comfortable at rest, but wherein ordinary physical activity        results in fatigue, shortness of breath, palpitations, or        angina. Class III corresponds to a marked limitation of physical        activity wherein, although patients are comfortable at rest,        even less than ordinary activity will lead to symptoms. Class IV        corresponds to inability to carry on any physical activity        without discomfort, wherein symptoms of CHF are present even at        rest and where increased discomfort is experienced with any        physical activity.

The change was made in order to clarify what the NYHA classes are. NYHAclasses are well-known to one of ordinary skill in the art (see, forexample. Col. 1, lines 49-64 of U.S. Pat. No. 6,645,153; Col. 3, lines11-29 of U.S. Pat. No. 6,045,513; paragraphs 8-11 of US 20020183584 A1)and the specification clearly sets forth using NYHA classes. Therefore,an inclusion of the definitions of the classes would not constitute newmatter.

Also included in each of the tables 720, 730 is a NYHA class column.Thus, NYHA class or left atrial pressure may be used to determine aweight for a patient and, in turn, a threshold. The NYHA classesgenerally pertain to congestive heart failure, which is often due toleft-sided dysfunction. For example, when the left ventricle is unableto pump out enough of the blood it receives from the lungs, pressureincreases inside the left atrium and then in the pulmonary veins andcapillaries, causing fluid to be pushed through the capillary walls intothe air sacs. Heart valve problems may also contribute to congestiveheart failure. For example, in mitral or aortic valve disease, thevalves that regulate blood flow either do not open wide enough (e.g.,stenosis) or do not close completely (e.g., aortic or mitral valveinsufficiency), which allows blood to flow backward through the valve.When the valves are narrowed, blood cannot flow freely into the heartand pressure in the left ventricle builds up, causing the left ventricleto work harder and harder with each contraction. The increased pressureextends into the left atrium and then the pulmonary veins, causing fluidto accumulate in the lungs. If a mitral valve leaks, some blood maybackwash toward the lung each time the heart pumps. If the leakagedevelops suddenly because of the snapping of the valve cord, a patientmay develop sudden and severe pulmonary edema.

While the tables 720, 730 provide two examples, various other mannersmay exist to determine one or more thresholds as described herein.Further, an exemplary method may include more than one threshold. Forexample, a percentage threshold may be used for a filling phase while aohms-days threshold may be used for a persistent edema phase associatedwith an increase in lung dry weight (e.g., due to fibrosis). While thethreshold (I_(OD)) is termed “ohms-days”, other impedance units or timeunits may be used.

While the tables 720, 730 include physiological parameters like LApressure and NYHA class, other parameters may be used as alternatives orin addition to LA pressure and/or NYHA class. For example, ejectionfraction, cardiac dimensions, cardiac output, evidence of mitralregurgitation, amount of body fluid, work test (e.g., 6 minute worktest), quality of life, etc., may be used together with weights,thresholds, ohm-days measures, etc. With respect to cardiac dimensions,one or more left ventricular dimensions may be used (e.g., peakdiastolic, peak systolic, etc.). Of course, LA or RV dimensions mayprovide relevant information. Further, change in a dimension withrespect to time may be used. For example, contraction dynamics for achamber (e.g., LV diameter or axial length over a cardiac cycle) may beused as an indicator of patient condition.

An exemplary method for determining a threshold for use in impedancemonitoring optionally uses echocardiograph information. Echocardiographinformation may pertain to cardiac function, pulmonary condition orboth. Thus, in a single echocardiograph session, a care provider maydetermine cardiac function and pulmonary condition of a patient. FIG. 8shows echocardiograph information from a study by Agricola et al.,“Ultrasound Comet-tail Images: A Marker of Pulmonary Edema”, CHEST 2005;127-1690-1695, which is incorporated by reference herein. The Agricolastudy analyzed echocardiograph information for the presence and thenumber of “sonographic Kerley lines” to detect and quantify pulmonaryedema.

The Agricola study performed echographic examinations of patients in thesupine position. In the study, ultrasound scanning of the anterior andlateral chest was obtained on both the right and left hemithorax, thesecond to fourth (on the right side to the fifth) intercostals space,and the parasternal to midaxillary line. In each intercostals space, thenumber of comet-tail images was registered at the parasternal,midclavear, anterior, and middle axillary lines. The sum of thecomet-tail images was provided as an echo comet score of theextravascular fluid of the lung. In the Agricola study, zero was definedas a complete absence of comet-tail images on the investigated area.

The Agricola study describes the comet-tail images as appearing whenthere is a marked difference in acoustic impedance between an object andits surroundings. In particular, the study notes that the reflection ofthe beam creates a phenomenon of resonance and the time lag betweensuccessive reverberations is interpreted as a distance, resulting in acenter that behaves like a persistent source, generating a series ofvery closely spaced pseudo-interfaces. A normal lung contains much airand little water on the lung surface, so with ultrasounds no densestructures are visible in normal subjects.

Agricola et al. defined the comet-tail image as a hyperechogenic,coherent bundle with narrow basis spreading from the transducer to thefurther border of the screen. The comet-tail image described by Agricolaextends to the edge of the screen (whereas short comet-tail artifactsmay exist in other regions), and arises only from the pleural line.Agricola et al. noted that comet-tail images arising from the pleuralline can be localized or disseminated to the whole lung surface, oragain isolated or multiple, with a distance less than or equal to about7 mm between two artifacts. Agricola et al. defined a positive (orpathologic) test result as bilateral multiple comet-tail images, eitherdisseminated (defined as all over the anterolateral lung surface) orlateral (defined as limited to the lateral lung surface). Whereas, anegative test result was defined as an absence of comet-tail images,replaced by the horizontal artifact, or when rare, isolated comet-tailimages were visible or when multiple comet-tail images were confinedlaterally to the last intercostal space above the diaphragm. TheAgricola study used an ultrasound system (Sonos 5500; Phillips MedicalSystems; Andover, Mass.) equipped with 1.8- to 3.6-MHz probe.

Agricola et al. scored echocardiograph information according to ascoring methodology. Using the methodology, thirty-two examinationresults were considered positive and 28 were negative. In a comparisonof test results considered positive versus negative, a significantdifference in mean extravascular lung water was found (742+/−277 mL vs392+/−92 mL, p<0.0001). The mean content of EVLW in negative test resultwas below the assumed normal limit of EVLW (<500 mL).

The plot 810 presents comet score versus EVLW data where a positivelinear correlation of R=0.42 (p<0.001) was found. The plot 820 presentscomet score versus wedge pressure data where a positive linearcorrelation of R=0.48 (p<0.001) was found. Agricola et al. note that thenumber of comet-tail images can provide an indirect measurement of wedgepressure and that such an indicator is advantageous because thecomet-tail images are detectable at a very early stage of pulmonaryedema, appearing below the conventional detection threshold of alveolaredema. Again, alveolar or airspace edema is always preceded byinterstitial edema, a constant feature of pulmonary edema.

An exemplary method uses echocardiograph information to determine athreshold for monitoring intrathoracic impedance. For example, such amethod may include acquiring echocardiograph information, determining adegree or phase of edema and then determining a threshold for use in animplantable monitoring device. The threshold may alert a patient or careprovider or cause other action. An exemplary method optionally uses morethan one threshold. In such an exemplary method, at least one of thethresholds may optionally rely on echocardiograph information.

The presence of existing lung fluid may indicate that any subsequentchange in impedance due to additional build-up of lung fluid will berelatively small whereas clearance of lung fluid may be an indicator ofimproved patient condition. An exemplary method optionally relates anincrease in impedance to an improved patient condition for a patientwith a deleterious preexisting level of lung fluid (e.g., a patienthaving pulmonary edema).

FIG. 9 shows an exemplary plot 910 of comet score versus weight andvarious exemplary relationships, equations or models 930 where a weightis a function of comet score and optionally one or more other factors.The exemplary plot 930 indicates that as comet score increases, theweight decreases. As already mentioned, the weight may be used to adjusta standard threshold used in impedance monitoring. The relationship ofthe plot 910 acts to adjust a standard threshold based on comet scorewhere a higher score indicates that a lower weight should be used andhence a lower threshold. For example, if a patient has symptoms ofpulmonary edema, then the threshold should be diminished such that asmall change in impedance acts to trigger an alarm or other action. Incontrast, a patient that has a low comet score, the relationship of theplot 910 assigns a higher weight whereby a larger change in impedancemust occur before an alarm or other action is triggered.

Any of the various exemplary equations 930 may be used to determine aweight based at least in part on comet score. For example, comet scorealone may be used or comet score in conjunction with one or more otherfactors such as, but not limited to, NYHA class, left atrial pressure(P_(LA)), and wedge pressure (P_(Wedge)).

FIG. 10 shows an exemplary method 1000 for determining a weight andcalculating a threshold based at least in part on the weight. Anexamination block 1004 includes examination of a patient or otherwiseacquiring patient data (e.g., left atrial pressure, NYHA class,echocardiograph information, etc.). The examination or acquiring patientdata may rely on invasive or non-invasive techniques. Further, suchinformation may come from a device implanted in the patient.

Once at least some patient data is available, a determination block 1008then relies on the patient data to determine a weight. In a calculationblock 1012, calculation of a threshold occurs based at least in part onthe weight. As already mentioned, the calculation may includemultiplying a weight and a standard threshold to provide an adjustedthreshold that accounts for patient condition or other patient relatedcharacteristics. In general, such a threshold is used in conjunctionwith impedance to determine patient condition. Impedance may beintrathoracic impedance, including intracardiac impedance.

An exemplary device (e.g., the device 100) includes a processor (e.g.,the programmable controller 220), an impedance measuring circuit (e.g.,the circuit 278) operably connected to the processor and control logic(e.g., various modules) operable in conjunction with the processor toacquire or determine a weight, to calculate a threshold based at leastin part on the weight and to compare the threshold to one or more of anintrathoracic impedance, a change in intrathoracic impedance, and aproduct of intrathoracic impedance and time. In such an exemplarydevice, the control logic may optionally make other comparisons. Inanother example, the calculation of a threshold may occur outside thedevice and the threshold communicated to the device (e.g., using adevice programmer). In various examples, the intrathoracic impedance isoptionally an intracardiac impedance.

FIG. 11 shows an exemplary system 1100 that includes a programmer 1110,an echocardiograph device 1120 and a communication path or network 1130.The programmer 1110 may have various features such as, but not limitedto, various features of the St. Jude Medical 3510 programmer (St. JudeMedical, Inc., Sylmar, Calif.). The programmer 1110 includes a paddle orwand 1114 for communication with an implantable device (e.g., considerthe device 100 of FIGS. 1 and 2). The programmer 1110 may rely on acommunications network 1130 to access or to receive information from theechocardiograph device 1120. The echocardiograph device 1120 may be usedto acquire echocardiograph information, which may be communicated to theprogrammer 1110 via the communication network 1130. The programmer 1110may implement one or more exemplary methods or rely on various exemplaryrelationships to determine one or more criteria for use in monitoringimpedance. Such criteria may be communicated to an implantable impedancemonitoring device using the paddle 1114 or other device (e.g.,telephone, etc.).

1. A method comprising: providing a New York Heart Association (NYHA) class of a patient; based on the NYHA class, determining a weight; based at least in part on the weight, determining a threshold for use in intrathoracic impedance monitoring of the patient; comparing an intrathoracic impedance of the patient to the threshold; and implementing control logic of a module, operable in conjunction with a processor, to decide, based on the comparing, whether to trigger a pulmonary edema alarm for the patient.
 2. The method of claim 1 wherein the intrathoracic impedance comprises an intracardiac impedance.
 3. The method of claim 1 wherein the threshold pertains to pulmonary edema occurring in a period of less than one day.
 4. The method of claim 1 wherein the threshold comprises a percentage decrease in intrathoracic impedance from a base value or baseline. 